Abstract 212P
Background
CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are the established first-line (1L) therapy for patients (pts) with hormone receptor (HR)-positive/HER2-negative (HR+/HER2-) metastatic breast cancer (mBC). Data supporting the best treatment choice at progression on CDK4/6i+ET is limited.
Methods
We collected data from pts with HR+/HER2- mBC who received treatment after progression to CDK4/6i+ET in five Italian Institutions. Progression-free survival 2 (PFS2), the primary endpoint, was calculated from initiation of CDK4/6i to disease progression (PD) on subsequent line of therapy or patient death. The PFS2-PFS1 difference and PFS2/PFS1 ratio were also estimated. We compared outcomes between pts receiving chemotherapy (CT)- or ET-based regimens immediately after CDK4/6i+ET.
Results
As of January 2023, 511 pts were included. Median patient age was 59 years, 26.2% had de-novo mBC. CDK4/6i were administered mostly in the 1L (62.8%) or 2L (24.5%) settings. Most pts received palbociclib (69.3%), followed by ribociclib (22.5%) and abemaciclib (8.2%). At PD, more pts received CT (60.7%) than ET (39.3%). There was a significant imbalance between the two groups in terms of visceral involvement (61.2% versus 43.8% of pts treated with CT and ET at PD, respectively; p=0.0001) and prior lines of therapy (CDK4/6i+ET was given 1L to 71% of pts who subsequently received ET and to 55.8% of pts who received CT; p=0.004). Median follow-up was 33 months (mo). After adjusting for evidence of visceral metastasis and prior therapy, mPFS2 was 23.5 mo and 18.5 mo in pts receiving ET and CT, respectively (adjusted HR 0.69, 95% CI 0.55-0.86, p=0.001). Median OS was longer in pts receiving ET than CT (58.1 vs 39.7 mo, adjusted HR 0.52, 95% CI 0.38-0.70, p<0.0001). However, PFS2-PFS1 curves did not differ between the two groups (p=0.594), and more pts receiving CT had a PFS2/PFS1 ratio≥1.3 (78.7 vs 54.3%, p<0.0001).
Conclusions
After progression to CDK4/6i, ET-based regimens are associated with longer PFS2 and OS when compared to CT. However, this likely reflects clinical benefit from previous CDK4/6i+ET. For pts with short PFS on CDK4/6i+ET, CT may be a more effective option.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
R. Caputo: Financial Interests, Personal, Other, Advisory or speaker bureau: Novartis, Lilly, Roche, AstraZeneca, MSD, Gilead, Daiichi Sankyo, Veracyte, Seagen, Pfizer, Eisai. C. Vernieri: Financial Interests, Personal, Invited Speaker: Novartis, Eli Lilly, Istituto Gentili; Financial Interests, Personal, Advisory Board: Novartis, Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Research Grant: Roche. E. Munzone: Financial Interests, Personal, Advisory Board: Eisai, Exact Science, MSD Oncology, Daiichi Sankyo/AstraZeneca, Pfizer, Seagen. M. Lambertini: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: Takeda, Sandoz, Ipsen, Libbs, Knight, Daiichi Sankyo, Lilly, Pfizer, Novartis, Roche; Financial Interests, Personal, Other, Travel grant to attend ASCO 2022: Gilead; Financial Interests, Institutional, Invited Speaker, 2-year research grant paid to my Institution: Gilead. M. De Laurentiis: Financial Interests, Personal, Invited Speaker, or honoraria: AstraZeneca, Amgen, Celgene, Daiichi Sankyo, Eisai, Eli Lilly, Exact Science, Gilead, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Seagen, Takeda, Ipsen; Financial Interests, Personal and Institutional, Funding: Novartis, Roche, Lilly, Puma Biotechnology, Pfizer, Daiichi Sankyo, MSD, MacroGenics, BMS. G. Viale: Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Speaker’s Bureau: Novartis, Lilly; Financial Interests, Personal, Other, Travel expenses: Pfizer, Lilly. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences, Celcuity; Financial Interests, Personal, Other, Advisory Board: Ellipsis; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Invited Speaker, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Invited Speaker, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Officer, Member of the Advisory Council: EUSOMA; Non-Financial Interests, Officer, ESMO Clinical Practice Guidelines Chair: ESMO. C. Criscitiello: Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, Eli Lilly, Roche, Gilead; Financial Interests, Personal, Advisory Board: MSD, Seagen, AstraZeneca, Daiichi Sankyo. All other authors have declared no conflicts of interest.